Cloning and functional expression of CC CKR5, a human monocyte CC chemokine receptor selective for MIP-1 alpha, MIP-1 beta, and RANTES

被引:255
作者
Combadiere, C [1 ]
Ahuja, SK [1 ]
Tiffany, HL [1 ]
Murphy, PM [1 ]
机构
[1] NIAID,HOST DEF LAB,NIH,BETHESDA,MD 20892
关键词
chemotaxis; inflammation; G protein;
D O I
10.1002/jlb.60.1.147
中图分类号
Q2 [细胞生物学];
学科分类号
071009 ; 090102 ;
摘要
We have cloned a human cDNA for a novel CC chemokine receptor (CC CKR) designated CC CKR5 that has 48-75% amino acid identity to other CC CKRs, CC CKR5 mRNA was detected constitutively in primary adherent monocytes but not in primary neutrophils or eosinophils, Macrophage inflammatory protein-1 alpha (MIP-1 alpha), MIP-1 beta, and RANTES were all potent agonists for CC CKR5 (EC(50) = 3-30 nM) when calcium flux was measured in transfected HEK 293 cells, yet the apparent binding affinities of the corresponding iodinated chemokines to intact cells expressing the receptor were low (IC50 similar to 100 nM). The calcium flux responses were completely blocked by treatment of transfected cells with pertussis toxin, These data suggest that CC CKR5 is a G(i)-coupled receptor that may mediate monocyte responses to MIP-1 alpha, MIP-1 beta, and RANTES.
引用
收藏
页码:147 / 152
页数:6
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